Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermia

Rosengren, Sanna; Mueller, James L.; Anderson, Justin P.; Niehaus, Brian L.; Misaghi, Amirhossein; Anderson, Scott; Boyle, David L.; Hoffman, Hal M.

doi:10.1016/j.jaci.2006.12.649

Cited by 53 publications

(50 citation statements)

References 29 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cold-induced inflammation seen in patients with FCAS was simulated ex vivo. Patient cells spontaneously released IL-1β in response to incubation at 32°C, a result that was blocked by anakinra, and that confirmed that modest cold exposure can trigger IL-1β release in these patients [21]. The role of mutant CIAS1-induced necrosis described in an in-vitro model needs further evaluation [22].…”

Section: Advances In Our Understanding Of the Pathophysiology Of Monomentioning

confidence: 81%

The spectrum of autoinflammatory diseases: recent bench to bedside observations

Ryan¹,

Goldbach‐Mansky

2008

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of review-The autoinflammatory diseases are a group of conditions that include the hereditary fever syndromes, and result from upregulated innate immune responses. The discovery of the genetic basis for these conditions led to the description of novel intracellular receptors for infectious and noninfectious danger signals. This article focuses on recent progress in our understanding of autoinflammatory syndromes, and how insights into these conditions have triggered the exploration of the role of innate immunity in common rheumatologic diseases.Recent findings-New models for the pathogenesis of several autoinflammatory syndromes have been proposed, including the role of pyrin and cryopyrin in regulating inflammation. Robust evidence has emerged that IL-1β oversecretion is pivotal in cryopyrin-associated periodic syndromes, and that IL-1 inhibition ameliorates the clinical features of these syndromes. Monosodium urate crystals stimulate IL-1β secretion via cryopyrin, which led to the addition of gout to the spectrum of autoinflammatory diseases.Summary-Advances in our understanding of the autoinflammatory diseases have led to renewed interest in the innate immune system, and its role in the pathogenesis of more common rheumatic diseases.

show abstract

Section: Advances In Our Understanding Of the Pathophysiology Of Monomentioning

confidence: 81%

The spectrum of autoinflammatory diseases: recent bench to bedside observations

Ryan¹,

Goldbach‐Mansky

2008

Current Opinion in Rheumatology

View full text Add to dashboard Cite

show abstract

“…Peripheral blood monocytes from patients with FCAS spontaneously secrete IL-1β when incubated at 32°C (14), as do murine cells harboring the L351P mutation (9). ELISAs for IL-18 demonstrated that FCAS CreT BMDCs, but not WT or MWS CreT BMDCs, also secrete IL-18 spontaneously when incubated at 32°C ( Figure 1B).…”

Section: Nlrp3 Mutant Mouse and Caps Patient Hematopoietic Cells Demomentioning

confidence: 96%

Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

Brydges¹,

Broderick²,

McGeough³

et al. 2013

J. Clin. Invest.

Self Cite

192

170

View full text Add to dashboard Cite

The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host-and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1-mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy.

show abstract

“…The infl ammasome is a multiprotein complex composed of a sensor NLR protein, the PYD-and CARD-domain containing adapter protein ASC, and the inflammatory protease caspase-1 (Martinon et al, 2002). Once activated, NLR changes conformation to recruit ASC and assemble the infl ammasome secrete IL-1β and IL-18, and IL-1 receptor antagonists have been proved to be an effective treatment for these autoinfl ammatory syndromes (Hoffman et al, 2004;Rosengren et al, 2007). Recently, increasing evidence indicates that dysregulated production of IL-1β are implicated in the pathophysiology of several common diseases, including atherosclerosis (Duewell et al, 2010), osteoarthritis (Denoble et al, 2011), metabolic syndrome (Strowig et al, 2012), and type 2 diabetes (Zhou et al, 2010).…”

Section: Introduction Of Inflammsomesmentioning

confidence: 99%

Negative regulation of NLRP3 inflammasome signaling

Chen

Sun

2013

Protein Cell

View full text Add to dashboard Cite

Infl ammasomes are multiprotein complexes that serve as a platform for caspase-1 activation and interleukin-1β (IL-1β) maturation as well as pyroptosis. Though a number of infl ammasomes have been described, the NLRP3 infl ammasome is the most extensively studied. NLRP3 infl ammasome is triggered by a variety of stimuli, including infection, tissue damage and metabolic dysregulation, and then activated through an integrated cellular signal. Many regulatory mechanisms have been identifi ed to attenuate NLRP3 infl ammasome signaling at multiple steps. Here, we review the developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage.

show abstract

Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermia

Abstract: These results confirm the central role of IL-1beta in FCAS and support the use of IL-1 targeted therapy in these patients.

Cited by 53 publications

References 29 publications

The spectrum of autoinflammatory diseases: recent bench to bedside observations

The spectrum of autoinflammatory diseases: recent bench to bedside observations

Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

Negative regulation of NLRP3 inflammasome signaling

Contact Info

Product

Resources

About